Vascular Signal Transduction Mechanisms
Gs-Protein Coupled Signal Transduction
Like heart muscle, the Gs-protein coupled pathway in smooth stimulates stimulates adenylyl cyclase (AC), which catalyzes the formation of cAMP. Unlike the heart, however, an increase in cAMP in vascular smooth muscle causes reduced contraction (i.e., relaxation). The reason for this opposite effect is that that calcium-calmodulin activates myosin light chain kinase (MLCK), which phosphorylates myosin and causes contraction; however, MLCK is inhibited by cAMP.
The Gs-protein is coupled to several important receptors that bind vasodilator substances, among which are β2-adrenoceptors (bind to β2-agonists such as epinephrine and isoproterenol), A2 purinergic receptors (bind to adenosine), and IP receptors (bind prostacyclin, PGI2).
IP3- Coupled Signal Transduction
cGMP-Coupled Signal Transduction
A third mechanism that is very important in regulating vascular smooth muscle tone is the nitric oxide (NO)-cGMP system. Vascular endothelial cells normally produce NO, which diffuses from endothelial cells to adjacent smooth muscle cells where it activates guanylyl cyclase leading to increased formation of cGMP and vasodilation. The precise mechanisms by which cGMP relaxes vascular smooth muscle is unclear; however, cGMP can activate a cGMP-dependent protein kinase, inhibit calcium entry into the vascular smooth muscle, activate K+ channels, and decrease IP3.
Acetylcholine (ACh), whether released by cholinergic autonomic nerves or exogenously administered, binds to muscarinic receptors on the vascular endothelium (muscarinic receptors in coronary vessels), which stimulates the formation and release of NO as described above to produce vasodilation. Certain antihypertensive and antianginal drugs are called nitrodilators because they release NO, and thereby mimic the effect of endothelial produced NO.